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Gyrodactylus spp. are common monogenean ectoparasites that may lead to significant fish mortality. To find effective anthelmintic agents with lower toxicity, a series of natural saponins were obtained and evaluated for their anthelmintic activity against Gyrodactylus kobayashii and acute toxicity to goldfish (Carassius auratus). Among all tested compounds, six compounds (1, 2, 3, 8, 10, and 13) shown higher anthelmintic activity and safety than widely used formaldehyde-based parasiticides, especially compound 1 having 100% anthelmintic efficacy against G. kobayashii at 0.3 mg/L and a therapeutic index of 16.6. Also, the three-dimensional quantitative structure-activity relationship (3D-QSAR) studies of these saponins have been performed to explore the structural features reasonable for the anthelmintic activity against G. kobayashii. These models demonstrated that the hydroxyl group at C-17 position and the sugar moieties at C-3 position, especially the hydroxyl groups of the sugar moieties, were critical to the anthelmintic activity. The QSAR studies could provide useful information for further rational design and optimization of novel saponins for the control of gyrodactylosis. [ABSTRACT FROM AUTHOR]

Gyrodactylid monogeneans are widespread parasites of teleost fishes, and infection with these parasites results in high host morbidity and mortality in aquaculture. To comprehensively elucidate the immune mechanisms against Gyrodactylus kobayashii, the transcriptome profiles of goldfish (Carassius auratus) skin after challenge with G. kobayashii were first investigated using next-generation sequencing. Approximately 21 million clean reads per library were obtained, and the average percentage of these clean reads mapped to the reference genome was 82.25%. A total of 556 differentially expressed genes (DEGs), including 344 upregulated and 212 downregulated genes, were identified, and 380 DEGs were successfully annotated and assigned to 95 signaling pathways in Kyoto Encyclopedia of Genes and Genomes (KEGG). In addition, 14 pathways associated with immune response were identified mainly including mTOR signaling pathway, cytokine-cytokine receptor interaction, intestinal immune network for IgA production, toll-like receptor signaling pathway, and phagosome. Twelve genes were selected and validated using qRT-PCR. A similar trend of these genes between RNA-Seq and qRT-PCR was observed, indicating that RNA-Seq data was reliable. Besides, the ALP activity and NO content in serum were significantly higher in the infected goldfish compared with the non-infected goldfish. In summary, this study provides better understandings of immune defense mechanisms of goldfish against G. kobayashii, which will support future molecular research on gyrodactylids and facilitate the prevention and treatment of gyrodactylosis in aquaculture. [ABSTRACT FROM AUTHOR]